The vertebrate immune system includes numerous proteins involved in the recognition and elimination of parasitic organisms. The general goals of this research are to understand the origin and evolution of key molecular components of this system, especially the molecules encoded by the genes of the major histocompatibility complex (MHC), and to understand the evolution of molecular adaptations in parasitic organisms that evade recognition and elimination by the host's immune system. The MHC is a multi-gene family encoding cell-surface glycoproteins, which play an important role in the immune system, binding foreign proteins and presenting them to T cells. Several of the MHC loci are highly polymorphic, and there is evidence that this polymorphism is maintained by balancing selection relating to most host immune surveillance. The methods used in this research involve statistical analysis of published DNA sequence data, of which a large amount is now available both for immune system genes and for genes of major human pathogens (particularly viruses). The purposes of these analyses are as follows: (1) to understand the evolutionary origin of MHC class I peptide-binding specificities; (2) to understand the evolutionary origin of MHC-related molecules that have assumed other functions; (3) to test the hypothesis that selection exerted by the host class I MHC and cytotoxic T cell (CTL) recognition system has played a role in the long-term evolution of viruses infecting vertebrates (including human immunodeficiency virus 1, hepatitis B virus, and papilloma viruses); (4) to understand the evolution of overlapping reading frames in viral genomes, with particular emphasis on the role of natural selection exerted by the host class I MHC/CTL recognition system on genes encoded by overlapping reading frames; (5) to understand the process by which the genomes of large DNA viruses (including adenoviruses, herpes viruses, poxviruses and baculoviruses) have "captured" host genes over the course of their evolution, a process which has enabled these viruses to obtain genes encoding immuno-modulating proteins which can interfere with host immune processes; and (6) to understand the evolution of repeat-containing proteins, which are believed to enable parasites to evade the highly specific recognition mechanisms of the host MHC and T cell system, in the genomes of the malaria parasites and DNA viruses.